Search

Objective: Vocal tremor (VT) poses treatment challenges due to uncertain pathophysiology. VT is typically classified into two phenotypes: isolated vocal tremor (iVT) and essential tremor-related voice tremor (ETvt). The impact of phenotypes on upper aerodigestive tract physiology during swallowing remains unclear. Qualitative and quantitative measures were employed to characterize tremor phenotypes and investigate the effects on swallowing physiology., Methods: Eleven ETvt participants (1 Male, 10 Female; x̄ age = 74) and 8 iVT participants (1 Male, 7 Female; x̄ age = 71) swallowed 20 mL boluses in cued and uncued conditions under standardized fluoroscopic visualization. Sustained/a/productions were captured to assess the rate and extent of fundamental frequency (F0) modulation. Penetration and Aspiration Scale (PAS) scores were obtained and swallowing biomechanics were captured using Swallowtail™ software. Participants also completed the Swallowing Quality of Life (SWAL-QOL) questionnaire., Results: Hypopharyngeal transit was faster in both VT phenotypes compared with Swallowtail™ normative reference data. Total pharyngeal transit times, however, were only faster in patients with iVT, relative to reference data. No significant differences were observed on the SWAL-QOL or PAS between tremor phenotypes. SWAL-QOL scores revealed that these patients rarely reported dysphagia symptoms., Conclusions: Subtle differences in swallowing patterns were observed across VT phenotypes, possibly related to adaptive mechanisms resulting in quicker pharyngeal bolus transit. Most patients did not report swallowing issues or dysphagia symptoms. This study is foundational for larger studies on this challenging population., Level of Evidence: 4 Laryngoscope, 134:4599-4603, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Neuropathic tremor occurs with damage to the peripheral nervous system. Guillain-Barré syndrome (GBS) causes acute paralysis following nerve inflammation sometimes resulting in long-term disability. It is unclear how frequent and severe tremor is following GBS., Objectives: We aimed to assess the frequency and features of tremor following GBS., Methods: We enrolled 18 patients with GBS treated in a secondary care center within a 4-year period. Evaluations were done with the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS). We compared these features with a cohort of consecutive patients with untreated essential tremor (ET)., Results: There were 13 males and 5 females with a mean age at evaluation (S.D.) of 41.5 ± 14.0 years and at GBS onset of 40.2 ± 13.7. No patient had history of tremor before GBS. Upper limb tremor was identified in 16 (89%) cases, 35.5% of patients had FTM-TRS score ≥10 points. Tremor was mostly kinetic, jerky with low amplitude with a total score of 10.94 ± 11.84 in the FTM-TRS. Compared with patients with ET, those with GBS-tremor were younger and had lower scores in all subscales of the FTM-TRS ( P value < 0.05 for all comparisons). In a multivariate linear regression analysis "days of hospitalization" had a positive association with the total FTM-TRS score ( P = 0.001)., Conclusions: Tremor was common following GBS. This tremor is mild compared with patients with ET, but adds functional impact., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background:  Patients often exhibit very severe or disabling forms of tremor that cannot be clearly characterized., Objective:  To present a series of 37 cases of tremor considered unclassifiable . Patients diagnosed with essential tremor according to criteria of the International Parkinson Disease and Movement Disorder Society (IPDMDS), who had been previously studied, were included as controls. All patients underwent a battery of tests between 2019 and 2022, which enabled us to compare them., Methods:  Relevant demographic and clinical information were collected. The following tools were applied: the Mini-Mental State Examination (MMSE); the Hospital Anxiety and Depression Scale (HADS); the Fahn-Tolosa-Marín Tremor Rating Scale (TRS); and the Quality of Life in Essential Tremor (QUEST). A simple brain magnetic resonance imaging (MRI) scan was performed for all patients. The categorical variables were compared using the Chi-squared test and the t -test with Fisher correction if appropriate, and the quantitative variables were compared through the two-tailed Student t -test. Values of p ≤ 0.01 were considered statistically significant., Results:  The cases presented higher scores on the anxiety and depression subscales of the HADS than the controls ( p ≤ 0.006 and 0.000 respectively). In all domains of the TRS, the cases scored significantly higher, as well as in the QUEST. History of enolism was higher among the controls, and history of orthostasis and rest tremor was higher among the cases ( p ≤ 0.000). Cerebellar atrophy was present in every patient in the case group, and in 24 subjects in the control group. Dystonia was observed in 7 subjects in the case group, and in none of the patients in the control group., Conclusion:  There are patients with unclassifiable and extremely disabling tremors who respond poorly to the pharmacological therapy options., Competing Interests: The author has no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: Tremor disorders remain as clinical diagnoses and the rate of misdiagnosis between the commonest non-parkinsonian tremors is relatively high., Objectives: To compare the clinical features of Essential Tremor without other features (pure ET), ET plus soft dystonic signs (ET + DS), and tremor combined with dystonia (TwD)., Methods: We compared the clinical features of patients with pure ET, ET + DS, and TwD enrolled in The ITAlian tremor Network (TITAN). Linear regression models were performed to determine factors associated with health status and quality of life., Results: Three-hundred-eighty-three patients were included. Sex distribution was significantly different between the groups with males being more represented in pure ET and females in TwD. The initial site of tremor was different between the groups with about 40% of TwD having head tremor and ET + DS unilateral upper limb tremor at onset. This pattern mirrored the distribution of overt dystonia and soft dystonic signs at examination. Sensory trick, task-specificity, and position-dependence were more common, but not exclusive, to TwD. Pure ET patients showed the lowest degree of alcohol responsiveness and ET + DS the highest. Midline tremor was more commonly encountered and more severe in TwD than in the other groups. Regression analyses demonstrated that tremor severity, sex, age, and to a lesser degree the variable "group", independently predicted health status and quality of life, suggesting the existence of other determinants beyond tremor., Conclusions: Pure ET and TwD manifest with a phenotypic overlap, which calls for the identification of diagnostic biomarkers. ET + DS shared features with both syndromes, suggesting intra-group heterogeneity., (© 2024 International Parkinson and Movement Disorder Society.)

Objective: The Cognitive Change Index (CCI-20) is a validated questionnaire that assesses subjective cognitive complaints (SCCs) across memory, language, and executive domains. We aimed to: (a) examine the internal consistency and construct validity of the CCI-20 in patients with movement disorders and (b) learn how the CCI-20 corresponds to objective neuropsychological and mood performance in individuals with Parkinson's disease (PD) or essential tremor (ET) seeking deep brain stimulation (DBS)., Methods: 216 participants ( N = 149 PD; N = 67 ET) underwent neuropsychological evaluation and received the CCI-20. The proposed domains of the CCI-20 were examined via confirmatory (CFA) and exploratory (EFA) factor analyses. Hierarchical regressions were used to assess the relationship among subjective cognitive complaints, neuropsychological performance and mood symptoms., Results: PD and ET groups were similar across neuropsychological, mood, and CCI-20 scores and were combined into one group who was well educated ( m = 15.01 ± 2.92), in their mid-60's ( m = 67.72 ± 9.33), predominantly male (63%), and non-Hispanic White (93.6%). Previously proposed 3-domain CCI-20 model failed to achieve adequate fit. Subsequent EFA revealed two CCI-20 factors: memory and non-memory ( p < 0.001; CFI = 0.924). Regressions indicated apathy and depressive symptoms were associated with greater memory and total cognitive complaints, while poor executive function and anxiety were associated with more non-memory complaints., Conclusion: Two distinct dimensions were identified in the CCI-20: memory and non-memory complaints. Non-memory complaints were indicative of worse executive function, consistent with PD and ET cognitive profiles. Mood significantly contributed to all CCI-20 dimensions. Future studies should explore the utility of SCCs in predicting cognitive decline in these populations.

Background: There is growing evidence that essential tremor (ET) patients are at high risk of cognitive impairment. Predictors of cognitive impairment have not been studied extensively. There is evidence from cross-sectional studies that sleep dysregulation is associated with cognitive dysfunction in ET, but longitudinal studies of the impact of sleep disruption on cognitive change have not been conducted. We investigated the extent to which sleep problems predict cognitive change in patients with ET., Methods: ET cases enrolled in a prospective, longitudinal study of cognitive performance. Sleep quality was assessed using the Pittsburg Sleep Quality Index (PSQI). Cognitive abilities across five domains (memory, executive function, attention, language, and visuospatial ability), and a global cognitive score (mean of the domains) were extracted from an extensive neuropsychological assessment. Generalized estimated equations were used to examine the association between baseline sleep problems and cognitive changes over three follow-up assessments each spaced 18 months apart., Results: The 188 non-demented ET cases had a mean age of 77.7 ± 9.5 years. Longer sleep latency was associated with longitudinal decline in executive function (p = 0.038), and marginally with longitudinal decline in global cognitive performance (p = 0.075). After excluding 29 cases with mild cognitive impairment, results were similar., Conclusion: Cognitively healthy people with ET who have longer sleep latency had greater declines in executive function during prospective follow-up. Early detection of, and possibly intervention for, abnormal sleep latency may protect against certain aspects of cognitive decline in ET patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Non-motor symptoms, including depression and cognitive impairment, are common in essential tremor (ET), but associations between these symptoms and tremor are poorly understood., Methods: A retrospective, single-institution, cohort study evaluated 140 patients with ET undergoing evaluation for deep brain stimulation (DBS) surgery. The Fahn-Tolosa-Marin (FTM) or Washington Heights-Inwood Genetic Study of ET (WHIGET) scale was used to grade tremor. Tremor scores were divided into quartiles. Patients underwent clinical neuropsychological evaluations that included a comprehensive cognitive test battery and Beck Depression Inventory-II (BDI-II). Subgroup analysis was performed with groups who met criteria for depression (BDI-II > 14) or overall cognitive impairment (<9th percentile on at least two dissimilar cognitive tests). Independent samples t-tests were used for continuous variables and chi square tests for categorical variables. Univariable and multivariable regressions were used to determine relationships between tremor and non-motor scores., Results: Tremor quartile was correlated with language domain performance (p = 0.044) but not depression scores. FTM score was associated with BDI-II (β = 0.940, p = 0.010), language (β = -0.936, p = 0.012), and visuospatial domain (β = -0.836, p = 0.025) scores, such that worse tremor was associated with more depression and worse language and visuospatial function. WHIGET score was not associated with any neuropsychological scores on multivariable regression., Conclusion: FTM score was associated with language, visuospatial, and mood symptoms, suggesting a relationship between the severity of these symptom types. Different tremor scores capture different motor symptoms and relationships with nonmotor symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Essential tremor (ET) is one of the most common neurological diseases. New evidence suggest that ET is associated with cognitive disorders other than motor symptoms. We aimed to investigate executive dysfunctions, which are comorbid cognitive deficiencies that may accompany ET. The study was conducted as an observational, case-control study in the Neurology Department of Ankara City Hospital in a 3-month period. The "Fahn-Tolosa-Marin Tremor Evaluation Scale" was used to rate tremor severity. Both patients and control group were subjected to the Mini Mental Test, followed by the Stroop TBAG test (TBAG is composed of the first letters of "TUBİTAK Temel Bilimler Araştırma Grubu," which means Scientific and Technological Research Council of Turkey Basic Sciences Research Group), word fluency (category fluency), phonemic fluency (K), and abstract thinking (binary similarities, proverb interpretation) tests. Both the patient and the control group consisted of 20 women and 20 men, with age, gender, and educational background compatible. Mean age of the patient group was 34.80 ± 13.23 years, while it was 34.95 ± 10.21 years in control group. In the ET group, statistically significant impairment was detected in the Stroop Test section 5 duration and error + correction number, category fluency, binary similarity, and phonemic fluency tests compared to the control group. There was a correlation between the severity of tremor and especially Stroop, category fluency, and binary similarity tests such that, as the severity of tremor increased, these test scores deteriorated. In ET patients, an impairment, accompanying tremor, may be present in executive functions that are a part of frontal lobe functions even in younger patients. This finding may suggest that impairment in the cerebellum-thalamus-frontal lobe connection may play a role in ET pathology.

Background: Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS., Objective: To evaluate the association between LC impairment and sleep disorders in ET and PD patients., Methods: A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC) and free-water value of LC (FWLC) with PSQI scores in ET and PD groups., Results: CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients., Conclusions: LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS.

Objective: Essential tremor (ET), while defined by progressive motor symptoms, is increasingly associated with cognitive impairments (e.g. attention, memory, and executive functions). This study characterizes the cognitive profile of individuals with ET on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a commonly-used neuropsychological screening measure. Method: Seventy-seven individuals (mean age: 70.6, 34% female) diagnosed with ET and being considered for surgical/procedural intervention were recruited from a Movement Disorders Clinic. All participants completed the RBANS, Grooved Pegboard Test (GPB), and Fahn, Tolosa, Marin Tremor Scale (FTMTS) in the clinical evaluation of their tremor. Results: One-sample t -tests found Immediate Memory, Language, Attention, and Total Scale Index scores to be significantly lower than the expected population mean ( p < .05). List Learning, Semantic Fluency, Coding, and List Recall subtests were significantly lower and Picture Naming was significantly higher than the expected population mean ( p < .05). GPB scores were correlated with the Attention Index as well as List Learning and Coding subtests. FTMTS Severity was correlated with the Coding subtest and FTMTS Disability was correlated with the Figure Recall subtest. Conclusions: Results support prior literature indicating cognitive weaknesses in those with ET. Individuals with ET had poorer global cognitive abilities, with specific decrements in Immediate Memory, Attention, and Language. Notably, the Attention Index and Coding subtest were most affected by motor functioning. Cognitive screening measures, like the RBANS, can efficiently identify strengths and weaknesses in individuals with ET seeking surgical/procedural interventions.

Background: Tremors other than those associated with Parkinson's disease (non-parkinsonian tremor) are commonly observed in clinical settings. However, their frequency and clinical characteristics have rarely been reported., Objectives: To classify non-parkinsonian tremors based on the consensus statement on the classification of tremors, from the task force of the International Parkinson and Movement Disorder Society published in 2018., Methods: A prospective registry at a tertiary care teaching institute., Results: A total of 475 patients with non-parkinsonian tremors were recruited for the study. 67.57% (n = 321) of our patients were male and a family history of tremor was present in 20.84% (n = 99) of patients. Dystonic tremor (DT) was the most common non-parkinsonian tremor (33.26%). 27.78% of patients fulfilled the new classification criteria for essential tremor, with 13.47% classified as pure ET (ET) and 14.31% exhibiting neurological soft signs, leading to the classification of ET plus (ETP). Patients with ETP had more family history (57.35%) [vs DT (26.48%, p = 0.00004) and ET (10.93%, p = 0.00003], longer duration of disease [mean ± standard deviation (SD) = 9.53 ± 8.64 years] [vs DT (5.60 ± 5.93, p = 0.0003) and ET (6.38 ± 5.97, p = 0.01) years], and more severe tremor as measured by the essential tremor rating assessment scale total score [mean ± SD = 27.42 ± 11.70] [vs DT (23.50 ± 8.62, p = 0.007) and ET (22.12 ± 8.19, p = 0.007)] compared with patients with DT and ET., Conclusions: DT was the most common cause of non-parkinsonian tremor in our registry followed by essential tremor syndrome. ETP was more common than ET., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Objective: Parkinson's disease (PD) and essential tremor (ET) involve neuroanatomical circuitry that impact frontal lobe functioning, via the striatum and cerebellum, respectively. The aim of this exploratory study was to investigate quantitative and qualitative performance between and within these groups on measures of verbal fluency. Method: Sixty-three PD and 53 ET patients completed neuropsychological testing. Linear regression models with robust variance estimation compared verbal fluency performance between groups related to correct responses and errors. Paired t -tests investigated within group error rates. Results: PD patients gave more correct responses for phonological ( β ̂   =5.3, p =.01) and category fluency ( β ̂   =4.1, p =.01) than ET patients; however, when processing speed was added as a covariate, this attenuated performance on both measures and only phonological fluency remained significant ( β ̂   =4.0, p =.04). There were no statistical differences in error scores between groups. Error rates within groups suggested that PD patients had higher error rates in total errors and perseveration errors on phonological fluency ( M  = 2.6, p =.00; M  = 1.6, p =.00) and higher total errors and set-loss error rates on category switching ( M  = 5.1, p <.001; M  = 4.1, p <.001). ET patients had higher error rate with relation to total errors and set-loss errors on phonological fluency ( M  = 2.5, p =.00; M  = 1.5, p =.02) and category switching ( M  = 3.9, p =,00; M  = 3.9, p <.001). Conclusions: PD patients performed better than ET patients on phonological fluency. PD patients appear to make more perseveration errors on phonological fluency, while ET patients made more set-loss errors. Implications for frontal lobe dysfunction and clinical impact are discussed.

Introduction: Parkinson's disease (PD) and essential tremor (ET) are two disorders known to lead to executive dysfunction, presumably through distinct pathways to the frontal lobes via the striatum or cerebellum, respectively. Memory functioning in PD and ET patients has been previously suggested to be adversely impacted by executive dysfunction. The aims of this exploratory study were to compare memory performance between and within groups on the California Verbal Learning Test - 3 (CVLT-3) through the analysis of core and process scores and to understand the relationship of these scores with measures of executive functioning., Method: Seventy PD and 54 ET patients completed comprehensive neuropsychological testing. Independent sample t-tests or Mann-Whitney tests were used to compare between group core and process scores on the CVLT-3. Within-subjects analyses were conducted via Wilcoxon Signed Rank Test due to nonparametric data. Spearman's correlations were conducted to explore the relationship between memory process scores and measures of executive functioning., Results: The ET and PD samples were similar with regard to age, education, gender, and general cognitive functioning. PD patients made more repetition errors ( U = 2391.50, p = .01) than ET patients and Normal Memory PD patients made more repetition errors than Low Memory PD patients ( U = 711.00, p = .00). Correlational analyses revealed repetition errors were negatively associated with tests of inhibition, set shifting, and working memory ( r s   = -.293, -.232). ET patients demonstrated a preference for a serial cluster learning strategy ( T = 861.00, p = .005), similar to PD patients ( T = 1633.00, p = <.001)., Conclusions: The study revealed presence of higher repetition errors in the PD sample that was demonstrated to have a negative relationship with measures of executive functioning. Implications for investigating process ("qualitative") scores in memory performance to determine extent of executive involvement are discussed.

Objective Given the association between essential tremor (ET) and higher rates of cognitive decline, assessing this decline is an important element of research and clinical care. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are two broad, brief measures that are widely used to monitor cognitive impairment in various neurological disorders. We sought to determine the relative ability of the MoCA and the MMSE to detect cognitive decline in elderly patients with ET. Methods We administered a neuropsychological battery to an ET cohort every 18 months over 4.5 years. We defined the gold standard for change in cognition as the change in neuropsychological test scores over consecutive evaluations and applied the Reliable Change Method to detect meaningful increases/decreases in test scores. We performed receiver operating characteristics (ROC) analysis to quantify the area under the curve (AUC) and compare the ability of the MoCA and the MMSE to detect cognitive decline. Results The AUCs for the MoCA and the MMSE did not differ significantly at any interval or when all intervals were pooled for analysis. Across all intervals, the ability of the MoCA and the MMSE to detect cognitive decline was consistently fair or poor. Conclusions We found that the ability of the MoCA and the MMSE to detect cognitive decline in ET patients over 18-month intervals is inadequate. Unchanged scores on the MoCA and the MMSE in ET over time should be approached with caution. We propose that these screening tools should be supplemented with additional neuropsychological tests.

Background: Although essential tremor (ET) is associated with cognitive decline, we know little about how specific cognitive changes predict significant events in patients' lives. We examined the relations of attention, executive function, language, memory, and visuospatial performance to the occurrence of near falls, falls, walking aid use, home health aide use, non-independent living and hospitalizations within a prospective, longitudinal study of ET cases. We expected executive function and memory to be most strongly associated with these events., Methods: 131 ET cases (mean age at baseline = 76.4 ± 9.4 years; 109 normal cognition; 17 mild cognitive impairment, 5 demented) completed questionnaires (clinical history and occurrence of life events) and a battery of neuropsychological tests at baseline and at 18, 36, and 54 months. We assessed associations between cognitive functioning and outcomes via regression equations., Results: Cases with lower baseline levels of executive function reported more near falls, p < 0.006, and were more likely to use a walking aid, p < 0.03, odds ratio (OR) = 2.89 during the follow-up period, than were other cases. Decline in executive function was associated with home health aide use during follow-up, p < 0.04, OR = 3.34. Baseline visuospatial performance also bore a marginally significant association with non-independent living arrangements during follow-up, p < 0.06, OR = 2.13. These effects were independent of age and tremor severity., Conclusion: These data establish the important role that cognitive decline, and executive function specifically, play in the experiences of ET patients. Moreover, these associations are of sufficient magnitude to have significant clinical implications., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Our study aimed to explore the associative relationship between neurodegenerative diseases and sleep disorders., Patients: This 15-year retrospective longitudinal nationwide population-based matched case-control study used data extracted from the National Health Insurance Research Database. We evaluated 25,589 patients diagnosed with neurodegenerative diseases between 2000 and 2015 and a matched control of 102,356 patients without neurodegenerative diseases., Results: Sleep disorders were an independent risk factor for the development of neurodegenerative diseases (adjusted odds ratio (OR): 1.794, 95% confidence interval (CI): 1.235-2.268, P < 0.001), with a positive dose-effect relationship (adjusted OR (95% CI): <1 year: 1.638 (1.093-2.872), P < 0.001; 1-5 years: 1.897 (1.260-3.135), P < 0.001; >5 years: 2.381 (1.467-3.681), P < 0.001. Moreover, patients with sleep disorder and comorbid depression had a significantly higher risk of neurodegenerative disorders (adjusted OR: 5.874). Subgroup analysis showed that insomnia was associated with Alzheimer's disease, Pick's disease and essential tremor (adjusted OR (95% CI): 1.555 (1.069-1.965), 1.934 (1.331-2.445) and 2.089 (1.439-2.648), respectively). Obstructive sleep apnea was associated with Parkinson's disease, essential tremor, and primary dystonia (adjusted OR (95% CI): 1.801 (1.239-2.275), 5.523 (3.802-6.977), and 4.892 (3.365-6.178), respectively). Other specific sleep disorders were associated with Pick's disease, Parkinson's disease, essential tremor, and primary dystonia (adjusted OR (95% CI): 8.901 (6.101-11.010), 1.549 (1.075-1.986), 2.791 (1.924-3.531), and 9.114 (6.283-10.506), respectively)., Conclusion: Sleep disorders are associated with the subsequent development of neurodegenerative disorders. Moreover, sleep disorder patients with comorbid depression have a higher risk of neurodegenerative diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: There is growing evidence that Parkinson's disease and diabetes are partially related diseases; however, the association between the two, and the impact of specific treatments, are still unclear. We evaluated the effect of T2D and antidiabetic treatment on age at PD onset and on all-cause mortality., Research Design and Methods: The standardized rate of T2D was calculated for PD patients using the direct method and compared with subjects with essential tremor (ET) and the general Italian population. Age at onset and survival were also compared between patients without T2D (PD-noT2D), patients who developed T2D before PD onset (PD-preT2D) and patients who developed T2D after PD onset (PD-postT2D)., Results: We designed a retrospective and prospective study. The T2D standardized ratio of PD (N = 8380) and ET (N = 1032) patients was 3.8% and 6.1%, respectively, while in the Italian general population, the overall prevalence was 5.3%. In PD-preT2D patients, on antidiabetic treatment, the onset of PD was associated with a + 6.2 year delay (p < 0.001) while no difference was observed in PD-postT2D. Occurrence of T2D before PD onset negatively affected prognosis (adjusted hazard ratio = 1.64 [95% CI 1.33-2.02]; p < 0.001), while no effect on survival was found in PD-postT2D subjects (hazard ratio = 0.86, [95% CI 0.53-1.39]; p = 0.54)., Conclusions: T2D, treated with any antidiabetic therapy before PD, is associated with a delay in its onset. Duration of diabetes increases mortality in PD-preT2D, but not in PD-postT2D. These findings prompt further studies on antidiabetic drugs as a potential disease-modifying therapy for PD., (© 2022. The Author(s).)

Background: Although Deep Brain Stimulation (DBS) is a safe and proven treatment modality for patients suffering from debilitating movement and neuropsychiatric disorders, it is not free from complications. Management of skin erosion and infection following DBS surgery constitutes a challenge in everyday clinical practice., Objectives: Skin-related complications were evaluated in patients who underwent DBS surgery due to Parkinson's disease (PD), dystonia, essential tremor (ET), and other indications including Tourette syndrome (TS), Obsessive-Compulsive Disorder (OCD), and epilepsy., Methods: A retrospective analysis of clinical data was performed on patients who underwent DBS surgery between November 2008 and September 2021 at the Department of Neurosurgery, Institute of Psychiatry and Neurology, Warsaw., Results: 525 patients who underwent 927 DBS leads implantations were included in the analysis. There were 398 patients with PD, 80 with dystonia, 26 with ET, 7 with drug-resistant epilepsy, 5 with Multiple Sclerosis, 4 with Holme's or cerebellar tremor, 3 with TS, and 2 with OCD. 42 patients (8,0%) had 78 skin infection episodes. The overall level of skin erosion was 3,8% (20/525 patients). The risk of developing infection episode was connected with younger age at diagnosis (p = 0.017) and at surgery (p = 0.023), whereas the development of skin erosion was connected with the dystonia diagnosis (p = 0.012). Patients with dystonia showed the highest rate of infections and erosions (11/70 and 7/70 patients retrospectively)., Discussion: Postoperative skin complications are a serious side effect of DBS surgery., Conclusion: Our study suggests that dystonic patients are at higher risk of developing skin-related complications after DBS surgery., Competing Interests: Conflict of interest The authors declare no potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: At the turn of the 21st century, closed-loop deep brain stimulation (CL-DBS) systems have emerged as promising neuromodulatory treatment strategies, that integrate real-time feedback based on the brain's condition to fine-tune the stimulation being applied. CL-DBS promises numerous advantages over open-loop deep brain stimulation (OL-DBS) systems. However, no up-to-date review articles are available which characterise the clinical outcomes of CL-DBS therapy., Methods: A systematic literature search was conducted in seven major databases with various keywords relating to CL-DBS, for non-randomised cohort studies, finalised clinical trials, case reports, and nonrandomised control trials published between 2011 and 2021., Results: Seven studies satisfied our inclusion criteria. Six investigated the use of CL-DBS therapy for neurological disorders, while one investigated its use for psychiatric disorders. The average patient age was 61 years (range: 27 - 78), and the mean disease duration before CL-DBS therapy was 15 years (range: 4 - 47). Patients included with essential tremor (ET) (n = 11) were older than patients with freezing of gait (FoG) in Parkinson's disease (PD) (n = 6) (p = 0.009), albeit insignificantly longer disease duration (p = 0.199). Following CL-DBS intervention, patients with ET (n = 11), major depressive disorder (n = 1) and Tourette syndrome (n = 1) had improvements in clinical outcomes, while PD patients had heterogeneous outcomes (n = 7). CL-DBS systems utilised by the included studies demonstrated a mean of 51.94 % (range: 36.62 - 68) energy-saving capacity over OL-DBS systems., Conclusions: To date, there is insufficient evidence that CL-DBS offers significant superior clinical outcomes over OL-DBS. Our scoping review suggests that CL-DBS can improve symptoms of specific neurological and psychiatric disorders, whilst demonstrating improved energy-saving capacity which has the potential to decrease battery replacement surgeries. Real-time adjustment of patients' symptoms using CL-DBS may improve patients' overall quality of life. Further studies are required to validate our observations., Competing Interests: Conflicts of interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Essential tremor (ET) is one of the most common movement disorders. The clinical heterogeneity of ET has been studied for many years, however, there are practically no comprehensive studies dedicated to the assessment of biochemical and electrophysiological parameters associated with the severity of motor and non-motor disorders present in patients with ET and taking into account their heterogeneity., Objectives: The objective of this report is to differentiate subgroups of essential tremor using cluster analysis of clinical, biochemical and electrophysiological parameters., Methods: The study enrolled 90 patients with ET. Clustering was perform on the demographic data, scores of scales FTMS, ADL, MoCA, Beka, surface electromyographic data, levels of serum IL-1β, IL-6, IL-8, IL-10, TNFα, uric acid, ceruloplasmin, MDA., Results: Based on the analysis of the severity of motor manifestations, the psychoemotional state, the adaptive potential of patients and the biochemical aspects of the pathogenesis, three relatively homogeneous clusters of ET were identified., Conclusions: Revealing the heterogeneity of essential tremor allows to expand understanding the pathogenesis of disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Mood symptoms are common features of Parkinson's disease (PD) and essential tremor (ET) and have been linked to worse cognition. The goals of the present study were to compare the severity of anxiety, apathy, and depressive symptoms in PD, ET, and healthy controls (HC) and to examine differential relationships between mood and cognition., Method: Older adults with idiopathic PD ( N = 448), ET ( N = 128), or HC ( N = 136) completed a multi-domain neuropsychological assessment consisting of memory, executive function, and attention/working memory domains. Participants also completed self-reported mood measures. Between-group differences in mood and cognition were assessed, and hierarchical regression models were conducted to examine relationships between mood and cognition in each group., Results: Relative to the HC group, the PD and ET groups reported more mood symptoms and scored lower across all cognitive measures. There were no differences between the two movement disorder groups. Mood variables explained 3.9-13.7% of the total variance in cognitive domains, varying by disease group. For PD, apathy was the only unique predictor of executive function ( β  = -.114, p = .05), and trait anxiety was the only unique predictor of attention/working memory ( β  = -.188, p < .05). For ET, there were no unique predictors, though the overall models significantly predicted performance in the executive function and attention/working memory domains., Conclusions: In a large cohort of ET and PD, we observed that the two groups had similar self-reported mood symptoms. Mood symptoms were differentially associated with cognition in PD versus ET. In PD, increased apathy was associated with worse executive function and higher trait anxiety predicted worse attention/working memory. For ET, there were no unique predictors, though the overall mood symptom severity was related to cognition. Our study highlights the importance of considering the relationship between mood and neuropsychological performance in individuals with movement disorders.

Background: Midline essential tremor (Mid-ET) is a distinctive group of essential tremor (ET) in which tremor affects the neck, jaw, tongue, and/or voice. For long, it has been considered as an ultimate stage of the disease and a marker of its severity. However, recent studies pointed its complexity in terms of non-motor presentation. Thus, we aimed to investigate the non-motor signs (NMS) in Mid-ET., Design: We conducted a cross-sectional study in a tertiary neurology referral center including ET patients classified into two groups based on the presence or not of midline tremor (Mid-ET vs. No-Mid-ET). We assessed NMS using the non-motor severity scale (NMSS), a large battery of cognitive tests, clinical and electrophysiological study of the autonomic nervous system along with the evaluation of sleep disturbances., Results: A total of 163 patients were included: Mid-ET (n = 79) and No-Mid-ET (n = 84) matched in gender and age of onset. Mid-ET patients had higher proportion of late-onset ET (> 60 years old, p = 0.002) and more extrapyramidal signs (p = 0.005). For NMS, Mid-ET was marked with cognitive dysfunction (p = 0.008). The hallmarks of the neuropsychiatric profile of Mid-ET were executive dysfunction (p = 0.004), attention problems (p < 0.000), episodic memory impairment (p = 0.003), and greater depression (p = 0.010). The presence of RBD was a trait of Mid-ET (p = 0.039). In both Mid-ET and No-Mid-ET phenotypes, clinical and neurophysiological dysautonomia correlated with cognitive dysfunction., Conclusion: Mid-ET patients had greater cognitive dysfunction, depression, RBD, higher proportion of late-onset ET, and more extrapyramidal signs. Taken all together, these findings could provide a redesigned insight into the underlying physiopathology of Mid-ET indicative of a greater cerebellar dysfunction., (© 2022. Fondazione Società Italiana di Neurologia.)

Objective: Essential tremor (ET) is a common neurological disorder that has been associated with 60% increased risk of developing dementia. The goals of the present study were to: (a) learn whether individuals with advanced ET symptoms seeking deep brain stimulation (DBS) surgery would fall into distinct cognitive subgroups, and (b) learn how empirically derived subgroups map onto criteria for mild cognitive impairment (MCI). Method: Patients with ET ( N  = 201; mean age = 68.9 ± 8.9 years) undergoing pre-surgical evaluation for DBS completed a multi-domain neurocognitive assessment consisting of memory, executive function, visuospatial skill, language, and processing speed. Two cluster analytic approaches ( K -means, hierarchical) were independently conducted to classify cognitive patterns using domain composites. Demographics, clinical characteristics, and proportion of cases meeting neuropsychologically defined criteria for MCI were examined among clusters. Results: A three-cluster solution reflected a Low Executive group ( N  = 64), Low Memory Multi-Domain group ( N  = 41), and Cognitively Normal group ( N  = 96). The Cognitively Normal group was older and more educated, with a higher Dementia Rating Scale-2 score. In total, 27.4% of participants met criteria for MCI. Of the MCI cases, most were in the Low Executive (41.8%) or Low Memory Multi-Domain groups (49.1%). In the latter, 65.9% of its members were classified as MCI versus 35.9% in the Low Executive group. Conclusions: Our study identified three cognitive subtypes of ET patients presenting for DBS. Future work should examine the subgroups for progression to dementia, particularly the Low Memory Multi-Domain subgroup which may be at highest risk.

Essential tremor (ET) is a prevalent neurological disorder with associated neuropsychological sequalae. Although cognitive deficits associated with ET are traditionally conceptualized as attention, processing speed, and executive impairments attributed to underlying frontal-subcortical dysfunction, emerging literature highlights the elevated frequency of progressive amnestic memory impairments in patients with ET. This case study centers around a 75-year-old woman with a 15-year history of ET who underwent deep brain stimulation (DBS) as well as three neuropsychological evaluations, one pre-surgically and two post-surgically at one and two-years post successful DBS surgery. Neuropsychological evaluation results revealed circumscribed mild and variable memory deficits pre-surgically and one-year post-surgically, However, two-years post-DBS, reliable change indices revealed significant declines in verbal/visual memory, consistent with an amnestic presentation, in addition to executive functions, aspects of higher-level language abilities, and overall IQ. This case study adds to a growing literature identifying a subset of ET patients with a neurodegenerative cognitive trajectory characterized by progressive, amnestic memory impairment. The case also highlights the importance of serial monitoring of cognition beyond the pre-surgical DBS workup to monitor for clinically significant decline(s).

Essential tremor (ET) is the most common movement disorder which has both motor and non-motor findings such as neuropsychiatic symptoms. Alexithymia is defined as inability to identify and describe emotions experienced by one's self or others. In our study, we aimed to evaluate the neurocognitive and brain micro-structural correlates of alexithymia in ET. 40 ET patients (mean age = 53.05 ± 19.74 years), were included. Fahn-Tolosa-Marin Tremor Rating Scale, Toronto Alexithymia Scale (TAS), Beck Depression Inventory, Beck Anxiety Inventory and detailed neurocognitive evaluation were applied to all patients. The patients were divided into three groups based on their TAS scores: no alexithymia, probable alexithymia, definite alexithymia. Diffusion Tensor Imaging (DTI) was performed in all patients. The mean TAS score was 50.05 ± 10.06. Depressive symptoms and anxiety levels were higher in definite alexithymia ( p  < 0.001, p  < 0.01). Partial correlation controlling for age, gender and educational level between alexithymia scores and each cognitive test showed significant association between similarities ( p  < 0.001) and phonemic verbal fluency ( p  = 0.04). Left orbitofrontal cortex average diffusion coefficient (ADC) value ( p  = 0.05), left anterior cingulate cortex fractional anisotropy (FA) value ( p  = 0.04), right cuneus FA value ( p  = 0.04), left amygdala ADC value ( p  = 0.01) and left insula ADC value ( p  = 0.02) were differed between groups. TAS and DTImetrics were not found to be independently associated with the level of anxiety ( p  < 0.001) and depressive symptoms ( p  < 0.01). As a conclusion, impairments in executive function and complex attention were correlated with higher levels of alexithymia in ET. Many micro-structural alterations were determined to be correlated with alexithymia levels.

Essential tremor (ET) is the most common cause of tremor in older adults. However, it is increasingly recognised that 30-50% of ET cases are misdiagnosed. Late-onset ET, when tremor begins after the age of 60, is particularly likely to be misdiagnosed and there is mounting evidence that it may be a distinct clinical entity, perhaps better termed 'ageing-related tremor'. Compared with older adults with early-onset ET, late-onset ET is associated with weak grip strength, cognitive decline, dementia and mortality. This raises questions around whether late-onset ET is a pre-cognitive biomarker of dementia and whether modification of dementia risk factors may be particularly important in this group. On the other hand, it is possible that the clinical manifestations of late-onset ET simply reflect markers of healthy ageing, or frailty, superimposed on typical ET. These issues are important to clarify, especially in the era of specialist neurosurgical treatments for ET being increasingly offered to older adults, and these may not be suitable in people at high risk of cognitive decline. There is a pressing need for clinicians to understand late-onset ET, but this is challenging when there are so few publications specifically focussed on this subject and no specific features to guide prognosis. More rigorous clinical follow-up and precise phenotyping of the clinical manifestations of late-onset ET using accessible computer technologies may help us delineate whether late-onset ET is a separate clinical entity and aid prognostication., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The new essential tremor (ET)-plus nomenclature was proposed by the 2018 Tremor Consensus Criteria. However, few studies have adopted this usage and the clinical differences between ET and ET-plus remains unclear. To address this issue, we reclassified and compared the characteristics of ET and ET-plus patients in a large Chinese tremor cohort., Methods: In this cross-sectional observational study, 766 patients originally diagnosed with ET underwent neurological examination. Scale ratings were used to evaluate motor and non-motor symptoms, and quality of life (QoL). We then reclassified the ET cohort and compared demographic and clinical characteristics between ET and ET-plus patients. A logistic regression analysis was used to explore whether the presence of neurological soft signs in ET-plus was associated with tremor severity or QoL., Results: Among 665 clinically confirmed ET syndrome patients, 274 were ET and 391 were ET-plus. The most prevalent neurological soft sign was resting tremor. ET-plus patients were older, had older age at onset and longer disease duration. ET-plus patients recorded higher scores in tremor severity evaluations and lower in cognitive evaluations, whereas a higher proportion of patients presented with depression or anxiety symptoms. Resting tremor and questionable cerebellar signs were associated with tremor severity. Cognitive impairment was associated with worse QoL., Conclusions: ET-plus patients were older, had longer disease durations, worse tremor manifestations, and more distinct non-motor symptoms. Certain additional soft signs of ET-plus were associated with tremor severity or worse QoL. ET-plus patients may include advanced ET patients with additional neurological soft signs presenting along with disease progression., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Movement disorders have different prevalence in different regions and they are little studied in Africa., Objectives: Evaluate the prevalence and determine the spectrum of movement disorders in the first specialized center in Senegal., Methods: It was a prospective study over on 18 months in adult outpatient clinic. Demographic, clinical, paraclinical data, including genetic test in collaboration with the Queen Square Institute of Neurology at UCL were collected., Results: One hundred and thirty four patients were followed up, representing a prevalence of 4.7%. Men represented 56% for a sex ratio of 1.3. The mean age of population was 47.7 ± 18 years with limits ranging from 16 to 81 years. Eighty-one patients (60.4%) had hyperkinetic and 53 patients (39.6%) had hypokinetic movements. Twenty-nine patients (21.6%) had tremors and 18 (13.4%) had dystonic movements. Ataxia and choreic movements were respectively in 11 (8.2%) and 10 patients (7.5%). Twenty-four patients (17.9%) were from a first-degree consanguineous. A genetic test on saliva samples was done in 16 patients (11.9%) and confirmed Huntington's disease in 8 patients of 6 families. Parkinson disease was the most frequent etiology (32.8%) followed by essential tremor (12.7%) and psychogenic tremor in 7.5%. Stroke accounted for 6% of the causes of MD (tremor, ballism, dystonia, ataxia and parkinsonism) and no etiology was found in 9%., Conclusion: The spectrum of movement disorders is very heterogeneous with a non-negligible frequency and diverse etiologies in neurological practice in Senegal., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Essential tremor (ET), a common movement disorder, is characterized by motor, cognitive and psychiatric symptoms. Depressed mood, a symptom of ET, has historically been viewed as a psychological response to disability. However, depressive symptoms are emerging as a predictor of cognitive decline across several clinical populations. We examined if depressive symptoms predict decline in global cognition, memory, and executive functioning among older adults with ET., Methods: 125 cognitively normal participants with ET completed three in-person assessments of cognition, mood, and motor symptoms at baseline, 18 months, and 36 months; baseline data were collected from July 2014-July 2016. Depressive symptoms were measured with the Geriatric Depression Scale. Cognitive functioning was measured via a 3-4 hour neuropsychological evaluation. Generalized linear regression models examined depressive symptoms as a predictor of decline in global cognition, executive functioning (EF), and memory., Results: Participants were grouped according to a median split (GDS <5 versus ≥ 5) due to the bimodal distribution of the data. In unadjusted models, depressive symptoms did not predict change in global cognition (b = -0.002, p = .502) or EF (b = 0.000, p = .931), however individuals with GDS ≥ 5 demonstrated faster memory decline in unadjusted (b = -0.008, p = .039) and adjusted models (b = -0.009, p = .019)., Conclusion: The presence of 5 or more depressive symptoms predicted mildly faster memory decline in cognitively normal older adults with ET over 36 months. We discuss potential mechanisms and clinical implications., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In 2018, the new Consensus Statement on the Classification of Tremors, by the Task Force on Tremor of the International Parkinson Movement Disorder Society, was published. So far, the article has been cited more than 400 times in peer-reviewed international journals and commonly debated in conferences and meetings due to an enthusiastic welcome from the community. Compared to the previous Consensus Statement (1998), the main novelties are: 1) the classification of tremor according to clinical manifestation (Axis 1) and etiology (Axis 2), and therefore the use of a syndromic approach; 2) the definition of essential tremor as a syndrome; 3) the recognition of the new category essential tremor plus, that derives from the uncertain significance of the soft neurological signs often associated with essential tremor. In this paper, we summarise and explain the most important aspects of the new classification of tremors, highlighting the main novelties, their relevance, and application in clinical practice. Moreover, we discuss its possible weakness and reflect on the critical comments made so far. We believe that this new tremor classification is comprehensive, rigorous, and consistent and, considering our current knowledge of tremor syndromes, it is the best we can do at present. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh., (Copyright © 2022. Published by Elsevier B.V.)

Tremor, the most common movement disorder, may occur in isolation or may co-exist with a variety of other neurologic and movement disorders including parkinsonism, dystonia, and ataxia. When associated with Parkinson's disease, tremor may be present at rest or as an action tremor overlapping in phenomenology with essential tremor. Essential tremor may be associated not only with parkinsonism but other neurological disorders, suggesting the possibility of essential tremor subtypes. Besides Parkinson's disease, tremor can be an important feature of other parkinsonian disorders, such as atypical parkinsonism and drug-induced parkinsonism. In addition, tremor can be a prominent feature in patients with other movement disorders such as fragile X-associated tremor/ataxia syndrome, and Wilson's disease in which parkinsonian features may be present. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna., (Copyright © 2021. Published by Elsevier B.V.)

Background: There is evidence that the risk of mortality is increased in patients with essential tremor (ET), however, there are few longitudinal, prospective data on the predictors of mortality in ET. There is also evidence that ET is associated with cognitive impairment; yet, it is unknown whether this is associated with elevated risk of mortality., Methods: In a longitudinal, prospective study of 194 elders with ET, an extensive neuropsychological test battery was performed at three time points: baseline, 18 months, and 36 months, and cognitive diagnoses (normal, mild cognitive impairment [MCI], and dementia) were assigned during consensus conferences. We used Cox proportional hazards models to estimate hazard ratios (HR) for death., Results: The mean baseline age was 79.1 ± 9.7 years. During follow-up, 52 (26.8%) died. In initial univariate models, a variety of baseline factors were associated with increased risk of mortality, including demographic variables (i.e., older age), cognitive variables and gait and balance variables. In the final multivariate Cox model, baseline dementia (HR = 2.66, p = 0.006), older baseline age (HR = 1.18, p < 0.001), and more reported falls at baseline (HR = 1.10, p < 0.001) were independently associated with increased risk of mortality. Amnestic MCI was marginally associated with increased risk of mortality (HR = 1.93, p = 0.08) in primary analyses and significantly (p < 0.05) in several sensitivity analyses., Conclusions: In this longitudinal, prospective study, baseline dementia resulted in a 2- to 3-times increase in risk of mortality in ET, further highlighting the clinical significance of cognitive impairment, specifically dementia, in this population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To determine how neuropsychiatric comorbidity, modulatory indication, demographics, and other characteristics affect inpatient deep brain stimulation (DBS) outcomes., Methods: This is a retrospective study of 45 months' worth of data from the National Inpatient Sample. Patients were aged ≥ 18 years old and underwent DBS for Parkinson Disease (PD), essential tremor (ET), general dystonia and related disorders, other movement disorder (non-PD/ET), or obsessive-compulsive disorder (OCD) at a US hospital. Primary endpoints were prolonged length of stay (PLOS), high-end hospital charges (HEHCs), unfavorable disposition, and inpatient complications. Logistic models were constructed with odds ratios under 95% confidence intervals. A p-value of 0.05 determined significance., Results: Of 214,098 records, there were 27,956 eligible patients. Average age was 63.9 ± 11.2 years, 17,769 (63.6%) were male, and 10,182 (36.4%) patients were female. Most of the cohort was White (51.1%), Medicare payer (64.3%), and treated at a large-bed size (80.7%), private non-profit (76.9%), and metro-teaching (94.0%) hospital. Neuropsychiatric comorbidity prevalence ranged from 29.9% to 47.7% depending on indication. Compared with PD, odds of complications and unfavorable disposition were significantly higher with other movement disorders and dystonia, whereas OCD conferred greater risk for HEHCs (p < 0.05). Patients with ET had favorable outcomes. Neuropsychiatric comorbidity, Black race, and Charlson Comorbidity Index > 0 were significantly associated with unfavorable outcomes (p < 0.05)., Conclusion: The risk of adverse inpatient outcomes for DBS in the United States is independently correlated with non-PD/ET disorders, neuropsychiatric comorbidity, and non-White race, reflecting the heterogeneity and infancy of widespread DBS for these patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Reduced diffusion along perivascular spaces in adults with Alzheimer's-disease-related-dementias has been reported and attributed to reduced glymphatic function., Objectives: To apply quantitative measures of diffusion along, and orthogonal to, perivascular spaces in a cohort of older adults with and without clinical symptoms of alpha-synuclein related neurodegeneration., Methods: 181 adults with Parkinson disease (PD) or essential tremor (ET) additionally sub-classified by the presence of cognitive impairment underwent 3 T MRI. Diffusion-tensor-imaging (spatial resolution = 2x2x2 mm; b-value = 1000 s/mm 2 ; directions = 33) measures of diffusion (mm 2 /s) parallel and orthogonal to perivascular spaces at the level of the medullary veins, and the ratio of these measures (ALPS-index), were calculated. Regions were identified by a board-certified neuroradiologist from T 1 -weighted and T 2 -weighted MRI. Evaluations of motor impairment and mild cognitive impairment (MCI) were interpreted by a board-certified neurologist and neuropsychologist, respectively. Multiple regression with false discovery rate correction was applied to understand how diffusion metrics related to (i) disease category (PD vs. ET), (ii) cognition (MCI status), and (iii) white matter disease severity from the Fazekas score., Results: The ALPS-index was reduced in PD compared to ET participants (p = 0.037). No association between the ALPS-index and MCI status, but an inverse association between the ALPS-index and Fazekas score (p = 0.002), was observed. The ALPS-index was inversely associated with age (p = 0.007)., Conclusion: Diffusion aberrations near perivascular spaces are evident in patients with alpha-synuclein related neurodegenerative disorders, and are related to age and white matter disease severity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: It has been debated for decades whether primary writing tremor is a form of dystonic tremor, a variant of essential tremor, or a separate entity. We wished to test the hypothesis that primary writing tremor and dystonia share a common pathophysiology., Objectives: The objective of the present study was to investigate the pathophysiological hallmarks of dystonia in patients affected by primary writing tremor., Methods: Ten patients with idiopathic dystonic tremor syndrome, 7 with primary writing tremor, 10 with essential tremor, and 10 healthy subjects were recruited. They underwent eyeblink classic conditioning, blink recovery cycle, and transcranial magnetic stimulation assessment, including motor-evoked potentials and short- and long-interval intracortical inhibition at baseline. Transcranial magnetic stimulation measures were also recorded after paired-associative plasticity protocol., Results: Primary writing tremor and dystonic tremor syndrome had a similar pattern of electrophysiological abnormalities, consisting of reduced eyeblink classic conditioning learning, reduced blink recovery cycle inhibition, and a lack of effect of paired-associative plasticity on long-interval intracortical inhibition. The latter 2 differ from those obtained in essential tremor and healthy subjects. Although not significant, slightly reduced short-interval intracortical inhibition and a larger effect of paired-associative plasticity in primary writing tremor and dystonic tremor syndrome, compared with essential tremor and healthy subjects, was observed., Conclusions: Our initial hypothesis of a common pathophysiology between dystonia and primary writing tremor has been confirmed. Primary writing tremor might be considered a form of dystonic tremor. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Introduction: Essential Tremor (ET) is increasingly recognized as a complex disorder with additional clinical signs other than tremor. It is still unknown whether a unique pathophysiologic or neurodegenerative process underlies progression and prognosis of the disease. The aim of the study was to identify ET phenotypes through a clinical-instrumental data-driven approach and to characterize possible patterns of neurodegeneration., Methods: ET patients were categorized using spatio-temporal and kinematic variables related to mobility and dynamic stability processed by motion transducers. Differences between the identified groups in clinical-demographic variables, neuropsychological performances and retinal parameters by Optical Coherence Tomography (OCT) segmentation analysis were tested., Results: Twenty-five ET patients were studied. Based on clustering of kinematic and spatio-temporal gait parameters, two independent groups were identified: cluster "A" (N = 15) and cluster "B" (N = 10). Compared to group A, group B had overall worse performance in mobility, especially on turning tasks. Identified clusters did not differ in terms of age, age at onset and disease duration. Patients in group B had more head tremor and more severe action tremor in the upper limbs as compared to group A, demonstrating also worse performances on cognitive assessments. Based on OCT analysis, group B presented a reduced thickness of the retinal inner layer as compared to group A, suggesting underlying neurodegenerative processes., Conclusions: The presence of gait and mobility impairment, associated with midline tremor, cognitive decline and retinal degeneration suggests a subtype of ET associated with neurodegeneration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Patients with essential tremor (ET) have an increased risk of cognitive impairment, yet little is known about the predictors of cognitive decline in these patients. Exposures to infectious agents throughout the lifespan may impact the later development of cognitive impairment. For example, high Infection exposure has been associated with lower cognitive performance in Alzheimer's and Parkinson's disease. However, this predictor has not been examined in ET., Objectives: To determine whether a higher baseline infection burden is associated with worse cognitive performance at baseline and greater cognitive decline over time in an ET cohort., Method/design: 160 elderly non-demented ET participants (80.0 ± 9.5 years) underwent an extensive cognitive evaluation at three time points. At baseline, participants completed an infection burden questionnaire (t-IBQ) that elicited information on previous exposure to infectious agents and number of episodes per disease. Analysis of covariance and generalized estimated equations (GEEs) were used., Results: Overall, infection burden was not associated baseline cognitive performance. Adjusted GEE models for repeated measures yielded a significant time interaction between moderate infection burden at baseline and better performance in the attention domain over time ( p = 0.013). Previous history of rubella was associated with faster rate of decline in visuospatial performance ( p = 0.046)., Conclusion: The data were mixed. Moderate self-reported infection burden was associated with better attention performance over time. Self-reported history of rubella infection was related to lower visuospatial performance over time in this cohort. Follow-up studies with additional design elements would be of value., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Purpose of the Review: Patients diagnosed with essential tremor (ET) report frequent sleep complaints. This review focuses on the main findings of studies addressing sleep features in patients diagnosed with ET, updating previously reported information. Bad quality of sleep and excessive daytime somnolence are very frequent in patients with ET, although the effects of the drugs used for the therapy of ET could contribute to these complaints. REM sleep behavior disorder, restless legs, insomnia, and nocturia are frequent complaints as well. There is a lack of studies addressing polysomnographic features of ET.

Objectives: To compare non-motor symptoms (NMSs) among patients with essential tremor (ET), Parkinson's disease (PD) subtypes (akinetic-rigid type (ART) and tremor-dominant type (TDT)), and healthy controls., Patients and Methods: This retrospective study included 129 participants, 72 PD (33 PD-ART, 33 PD-TDT, and 6 Mixed), 29 ET patients, and 28 controls. PD patients were assessed by the unified Parkinson's disease rating scale (UPDRS), Hoehn, and Yahr scale (H&Y), while ET patients were evaluated by the Fahn Tolosa Marin Tremor Rating Scale. All subjects were evaluated by non-motor symptoms scale (NMSS) for NMSs and Beck depression inventory (BDI) for depression., Results: PD subtypes groups, ET, and controls were age and gender-matched. Compared to controls, all PD, PD subtypes, and ET showed significantly worse most of NMSs (p<0.001) and depression. Compared to ET, all PD and PD-ART had significantly worse gastrointestinal (p = 0.002), urinary symptoms (p = 0.001, p = 0.003) and depression (p = 0.002) and PD-TDT worse depression, while ET patients showed worse memory/attention than PD subtypes. Total NMSS of ET is highly correlated to depression and moderately to tremor severity and age of onset, while total of NMSS is highly correlated to depression, disease severity, and disability., Conclusion: The current study demonstrated several comparable domains of NMSs of PD subtypes and ET, except worse gastrointestinal and urinary symptoms among PD-ART. Identifying different NMSs profiles is important for predicting, better assessing, and tailoring management of ET and PD subtypes., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Essential tremor (ET) patients presenting tremor in the midline structures may be a distinct subtype of the syndrome. Therefore, we sought to explore the clinical manifestations, especially non-motor symptoms (NMS) of Chinese ET patients with midline tremor (MT)., Methods: In the cross-sectional study, we grouped 290 definite or probable ET patients based on their MT conditions. The NMS in ET patients were evaluated using the NMS scale (NMSS). NMS and other clinical correlates were then compared among subgroups with, and without MT., Results: We revealed that 39.0%, 27.6%, and 6.9% of the patients respectively had neck, voice, and facial tremors. With the accumulation of tremor in midline structures, NMS became more severe and prevalent. Logistic regression analyses revealed that factors such as: female gender (OR = 2.164, 95% CI: 1.307-3.583), having least or highest action arm tremor (OR = 2.512, 95% CI: 1.520-4.151), having higher score of sleep/fatigue domain (OR = 1.692, 95% CI: 1.004-2.850) and mood/apathy (OR = 1.926, 95% CI: 1.143-3.246) domain, to be independently associated with MT manifestation., Conclusions: Our study demonstrates the heterogeneity of symptoms in ET patients with MT, especially in prominent NMS. In addition, the discrepancy of NMS between patients with, and without MT provides novel insight into the underlying pathophysiology and therapeutic of ET., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Sleep disorders are frequent in patients diagnosed with essential tremor (ET). The present review focuses on sleep disorders and the results of polysomnographic studies performed in patients with ET. For this purpose we performed a systematic review crossing the search term "essential tremor" with "sleep," "sleep disorders," "sleep disturbances" and "polysomnography," and with specific sleep disorders, according to the International Classification of the Sleep Disorders-Third Edition, using the PubMed, EMBASE, MEDLINE, and Web of Science Databases. The most frequent sleep problems reported by patients with ET were the bad quality of sleep and excessive daytime somnolence (the latter could be related to drugs commonly used for the treatment of ET). Probable rapid eye movement sleep behavior disorder, coexistent restless legs syndrome, insomnia, and nocturia were not infrequent complaints, while the presence of other sleep disorders in patients with ET was restricted to anecdotal reports or not described. Meta-analyses of previous reports showed that patients with ET (according to the PRISMA and MOOSE guidelines) showed higher scores in the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale than controls and lower scores than those of patients diagnosed with Parkinson's disease. Studies using polysomnography in patients with ET are scarce and do not permit to establish valid conclusions regarding polysomnographic features in this disorder., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: There have been few comprehensive scale studies on the non-motor symptoms (NMS) of patients with essential tremor (ET) with head tremor (ETh) and those with ET without head tremor (ETol). We aimed to explore the motor symptoms and NMS of these two subgroups., Methods: We enrolled 199 patients with ET (125, ETol; 74 ETh) and 132 healthy controls. We evaluated motor symptoms using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and NMS using the Non-Motor Symptom Scale (NMSS). We compared NMSS scores and the prevalence of each NMS between the patient subgroups. Finally, we conducted a logistic regression analysis of the correlation between head tremor and NMS severity, as well as other determinants., Results: There were no significant between-subgroup differences in demographic characteristics. Further, they presented similar tremor clinical manifestation; however, the ETh subgroup showed a higher prevalence of rest tremor, feeling of sadness, forgetting things or events, and swallowing difficulty, as well as TRS scores, compared with the ETol subgroup. Both patient subgroups showed high scores and prevalence (>50%) in difficulty falling asleep. Logistic regression analysis indicated age as a tremor severity determinant; further, head tremor and tremor severity were NMS determinants., Conclusion: Both patient subgroups presented various NMS including sleep disturbances, cognitive deficits, and affective disorders. The ETh subgroup showed a high prevalence of certain NMS aspects including memory and affective disorder; further, they had aggravated NMS. ET with both upper limb tremor and head tremor may be regarded as a more severe clinical subtype., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Essential tremor (ET), among the most common neurological diseases, is associated with cognitive dysfunction. Yet, nearly all knowledge of ET-related cognitive impairment is static and cross-sectional (e.g., prevalence), with virtually no dynamic information (i.e., course and progression, conversion rates, and clinical outcomes)., Objectives: To quantify the rate of progression from mild cognitive impairment (MCI) to dementia in a cohort of elderly ET cases., Methods: 167 ET cases, enrolled in a prospective, longitudinal, clinical-pathological study, underwent an extensive neuropsychological testing battery at baseline (T1), 1.5 years (T2), and 3 years (T3). Results of these assessments informed clinical diagnoses of normal cognition (ET-NC), MCI (ET-MCI), and dementia (ET-D)., Results: At baseline, 26 cases (82.7 ± 7.7 years) were diagnosed with ET-MCI and were available for follow-up at T2. At T2, three of 26 (11.5%) had converted to ET-D. At the start of T2, 23 cases (83.6 ± 7.7 years) were diagnosed with ET-MCI and were available for follow-up at T3. At T3, six of 23 (26.1%) converted to ET-D. The average annual conversion rate from ET-MCI to ET-D was 12.5%., Conclusions: The study of cognitive impairment in ET is a nascent field, with limited data. We show that the conversion rate from ET-MCI to ET-dementia was 12.5%. Available studies on historical controls have reported conversion rates of 2.6-6.3%. Data such as these systematically fill gaps in knowledge, creating a scientifically-derived knowledge base to guide physicians and patients in clinical settings., Competing Interests: Declaration of competing interest There are no conflicts of interest or competing financial interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: There is growing evidence that a proportion of patients with Essential Tremor (ET) may develop a memory impairment over time. However, no studies have evaluated whether hippocampal damage really occur in ET. This study investigated the macro and micro-structural integrity of the hippocampus in ET subjects using a multimodal MRI approach., Methods: Neuropsychological and MRI data were acquired from 110 participants (60 patients with ET and 50 age-, sex-, and education-matched healthy controls [HC]). Whole-brain T1-weighted and Diffusion Tensor Imaging (DTI) were performed to assess macro-and microstructural alterations. MRI parameters (volume; mean diffusivity [MD]; fractional anisotropy [FA]) of bilateral hippocampi were obtained. In order to evaluate the relationship between MRI alterations and neurocognitive impairment, hippocampal parameters were also correlated with cognitive test scores., Results: Compared to controls, ET patients showed a subclinical memory impairment with significantly lower memory scores, but within the normal ranges. Despite the subclinical damage, however, ET patients showed a significant increase in MD values in the bilateral hippocampi in comparison with HC. A significant correlation was also found between MD and memory scores in ET., Conclusion: This study improves the knowledge on memory impairment in ET, as our results demonstrate for the first time the hippocampal microstructural damage related to subclinical memory impairment in ET patients. Further studies are needed before these findings can be considered predictive of a distinct ET subtype or suggestive of a co-occurent dementia., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose. None of the authors have received financial support or funding for the research covered in this article., (Copyright © 2020. Published by Elsevier Ltd.)

Optical coherence tomography (OCT) has been suggested as a method for detection of retinal alterations in neurodegenerative diseases. The usefulness of OCT as a diagnostic tool to differentiate Parkinson's disease (PD) from other tremor diseases, remains unknown. We aimed to evaluate morphological changes of the retina in patients with PD, essential tremor (ET), essential tremor-Parkinson's disease (ET-PD) using OCT. Forty-two eyes of 21 patients with PD, 24 eyes of 12 patients with ET, 24 eyes of 12 patients with ET-PD and 44 eyes of 22 age-matched healthy controls were included in the study. All participants underwent detailed neurological and ophthalmological examination. Measurements in all quadrants of macula and retinal nerve fiber layer (RNFL) thickness using OCT were recorded. There was no significant difference among the groups regarding age, sex. The average RNFL thickness was thinner in PD patients than that of ET (p = 0.032). The RNFL thickness in superior quadrant was lower in PD group compared with the ET and control group (p = 0.001, p = 0.016). Significant differences were observed in most of the macular thickness parameters excluding foveolar and foveal thickness (p = 0.865, 0.394). Correlations were found among several OCT parameters and disease duration or severity in all patient groups (p > 0.05). Retinal alterations were found in PD patients compared to ET. However, no significant retinal changes were detected by OCT in patients with ET and ET-PD compared to controls. According to our data, retinal assessments by OCT do not seem to be satisfactory for differentiation of these disorders.

Background: Unilateral or very asymmetric upper limb tremors with a jerky appearance are poorly investigated. Their clinical classification is an unsolved problem because their classification as essential tremor versus dystonic tremor is uncertain. To avoid misclassification as essential tremor or premature classification as dystonic tremor, the term indeterminate tremor was suggested., Objectives: The aim of this study was to characterize this tremor subgroup electrophysiologically and evaluate whether diagnostically meaningful electrophysiological differences exist compared to patients with essential tremor and dystonic tremor., Methods: We enrolled 29 healthy subjects and 64 patients with tremor: 26 with dystonic tremor, 23 with essential tremor, and 15 patients with upper limb tremor resembling essential tremor but was unusually asymmetric and jerky (indeterminate tremor). We investigated the somatosensory temporal discrimination threshold, the short-interval intracortical inhibition, and the cortical plasticity by paired associative stimulation., Results: Somatosensory temporal discrimination threshold was significantly increased in patients with dystonic tremor and indeterminate tremor, but it was normal in the essential tremor patients and healthy controls. Significant differences in short-interval intracortical inhibition and paired associative stimulation were not found among the three patient groups and controls., Conclusion: These results indicate that indeterminate tremor, as defined in this study, shares electrophysiological similarities with dystonic tremor rather than essential tremor. Therefore, we propose that indeterminate tremor should be considered as a separate clinical entity from essential tremor and that it might be dystonic in nature. Somatosensory temporal discrimination appears to be a useful tool in tremor classification. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

DBS of the ventral intermediate nucleus is an extremely effective treatment for essential tremor, although a waning benefit is observed after a variable time in a variable proportion of patients (ranging from 0% to 73%), a concept historically defined as "tolerance." Tolerance is currently an established concept in the medical community, although there is debate on its real existence. In fact, very few publications have actually addressed the problem, thus making tolerance a typical example of science based on "eminence rather than evidence." The underpinnings of the phenomena associated with the progressive loss of DBS benefit are not fully elucidated, although the interplay of different-not mutually exclusive-factors has been advocated. In this viewpoint, we gathered the evidence explaining the progressive loss of benefit observed after DBS. We grouped these factors in three categories: disease-related factors (tremor etiology and progression); surgery-related factors (electrode location, microlesional effect and placebo); and stimulation-related factors (not optimized stimulation, stimulation-induced side effects, habituation, and tremor rebound). We also propose possible pathophysiological explanations for the phenomenon and define a nomenclature of the associated features: early versus late DBS failure; tremor rebound versus habituation (to be preferred over tolerance). Finally, we provide a practical approach for preventing and treating this loss of DBS benefit, and we draft a possible roadmap for the research to come. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)